FM DECEMBER 2018 ISSUE - digital edition

investigational prodrug of temsavir, is an attachment inhibitor
of HIV-1.
Results from the 48-week data showed that 54%
of patients in the randomised cohort achieved virologic
suppression on treatment with fostemsavir plus optimised
background therapy. Additionally, patients in the randomised
cohort showed immunologic improvement through week 48 as
demonstrated by an increase in CD4+ T-cell counts.
"We are moving towards medicines with new mechanisms
of action and long-acting formulations, as we think about more
options for patients and making HIV a smaller part of their
lives," says Dr Pottage.
In addition to fostemsavir, ViiV is pursuing maturation
inhibitors and biologics and is partnering with University of
North Carolina HIV Cure Center.
Towards a functional cure?
Abivax, a clinical-stage company headquartered in Paris, is
currently working on an approach that seeks to block the viral
RNA's ability to multiply.
Experimental drug candidate ABX464 is an oral small
molecule that inhibits HIV replication through an entirely new
mechanism of action. In two Phase 2a clinical trials, ABX464
demonstrated up to 50% reduction of HIV-DNA in peripheral
blood mononuclear cells after 28 days of combination
treatment with ART.
Pre-clinical data suggest that ABX464 has the potential
to reduce or eliminate the viral reservoirs in patients with
HIV, thus delivering long-term control of the viral load and
preventing the emergence of HIV mutants that are resistant to
treatment after six months of treatment in vitro. It also offers
the advantages of less frequent dosing.
``The biggest problem with current therapies in HIV is
that they are unable to reduce the viral reservoir of HIV that
lies latent in human immune cells. The viral reservoir is the
integrated viral DNA within infected cells that perpetuates the
production of viruses,'' says an Abivax spokesperson.
Though ART can keep active viruses out of the
bloodstream, existing reservoirs, or HIV “factories”, cannot be
affected by ART. Therefore, if ART is terminated even for a short
time, a viral rebound can occur.
ABX464 has a particular mechanism of action in HIV that
is two-fold. Viral DNA integrated into infected cells codes for
viral proteins that the cell is “tricked” into producing during
translation. ABX464 is believed to inhibit a protein that is
necessary for the shuttling of certain viral proteins out of
the nucleus, thus preventing viruses from being reproduced
within infected cells. ABX464 also induces splicing of certain
sequences of viral RNA, the molecular products of which signal
the immune system to attack the cells which are infected,
according to the spokesperson.
Abivax believes the drug can offer a functional cure
for HIV by way of this mechanism. That means the virus
can be controlled without the need for ART, and not a
PREP: A DAILY PILL
TO PREVENT HIV
P
re-exposure prophylaxis (PrEP) is
a combination of tenofovir and
emtricitabine. It is approved for daily
use to help prevent an HIV-negative
person from getting HIV from a sexual
or injection-drug-using partner who is
positive. USFDA has approved the pill
for HIV-negative adults and adolescents
weighing at least 35 kg.
Daily PrEP use can lower the risk of
getting HIV from sex by more than 90%
and from injection drug use by more
than 70%.
The WHO has recommended
PrEP for all groups at risk of infection.
Randomised controlled trials have
shown that rapid, targeted, and highcoverage
roll-out of PrEP can have a
large and fast impact on people at risk.
PrEP was approved in 2012 in the
US. The uptake, however, was slow at
the beginning. By late 2016, as many
as 83,672 men in the US had started on
PrEP, according to estimates.
The NHS announced it would
provide PrEP to 10,000 patients
in selected clinics in England from
September 2017. There was a marked
decline in HIV diagnoses in the same
year, following the introduction of PrEP.
In France, roughly 97% of men
who have sex with men (MSM) (2,805
people) were commenced on PrEP in
the first 12 months of roll-out in 2016.
Only four new HIV infections in this
cohort were reported.
DECEMBER 2018 / FUTURE MEDICINE / 25